Polymerized shell lipid microbubbles and uses thereof

Abstract

The present invention relates to the fabrication and use of microbubbles. In some embodiments, the invention provides for the fabrication and use of polymerized shell lipid microbubbles (PSMs). The microbubbles of the invention can be used, for example, for diagnosis and treatment of a condition.

1 . A microbubble comprising a polymerized lipid shell and a gas, wherein the gas is encased within the shell, and wherein the polymerized lipid shell comprises at least about 5% polymerizable lipid. 
     
     
         2 . (canceled) 
     
     
         3 . The microbubble of  claim 1 , wherein the gas is a perfluorocarbon. 
     
     
         4 . The microbubble of  claim 3 , wherein the perfluorocarbon is decafluorobutane. 
     
     
         5 . The microbubble of  claim 1 , wherein the gas is a mixture of at least two perfluorocarbons. 
     
     
         6 . The microbubble of  claim 1 , wherein the polymerized lipid shell comprises at least one polymerizable lipid and at least one non-polymerizable lipid and has a percentage of about 5-50% polymerizable lipid. 
     
     
         7 . The microbubble of  claim 6 , wherein the at least one non-polymerizable lipid is L-α-phosphatidylcholine), PE-PEG2000 (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000 or PE-PEG2000-biotin. 
     
     
         8 . The microbubble of  claim 6 , wherein the at least one polymerizable lipid is a diacetylenic lipid. 
     
     
         9 . The microbubble of  claim 6 , wherein the microbubble is UV treated for about 2-5 minutes after fabrication to polymerize the lipid shell. 
     
     
         10 . (canceled) 
     
     
         11 . The microbubble of  claim 1  wherein the microbubble was prepared by a microfluidic flow focusing device. 
     
     
         12 . The microbubble of  claim 1  wherein the microbubble comprises a targeting agent. 
     
     
         13 . (canceled) 
     
     
         14 . (canceled) 
     
     
         15 . (canceled) 
     
     
         16 . The microbubble of  claim 1 , wherein the microbubble is an ultrasound contrast agent further comprising an acceptable carrier for administration to an individual. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . A collection of microbubbles comprising gas-filled polymerized shell lipid microbubbles, wherein the microbubbles in the collection are monodispersed and are within 2-5 μm size range. 
     
     
         20 . (canceled) 
     
     
         21 . The collection of  claim 19 , wherein the microbubbles in the collection comprise at least about 5% polymerizable lipid. 
     
     
         22 . (canceled) 
     
     
         23 . A method of treating an individual comprising:
 administering a microbubble to an individual in need of thereof, said microbubble comprising a polymerized lipid shell, a gas, a targeting agent and a therapeutic agent, wherein the gas is encased within the shell, and wherein the polymerized lipid shell comprises at least about 5% polymerizable lipid.   
     
     
         24 . (canceled) 
     
     
         25 . (canceled) 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . (canceled) 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . A method of making a microbubble of  claim 1  comprising:
 (a) microfluidic flow focusing a mixture of polymerizable lipid and standard non-polymerizable lipid and a gas through an aperture to form micrometer microbubbles and (b) UV treating the microbubbles of step a for at least 2 minutes to polymerize the polymerizable lipid. 
 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . The method of  claim 33 , wherein the mixture of lipids comprises at least one polymerizable lipid and at least one non-polymerizable lipid. 
     
     
         39 . The method of  claim 33 , wherein the polymerizable lipid makes up a percentage of about 5-50% of total lipid of the mixture. 
     
     
         40 . The method of  claim 33 , wherein the non-polymerizable lipid is L-α-phosphatidylcholine), PE-PEG2000 (1,2-distearoyl-sn-glycero-3-phosphoethanolatnine-N-[methoxy(polyethylene glycol)-2000 or PE-PEG2000-biotin. 
     
     
         41 . The method of  claim 39 , wherein the polymerizable lipid is a diacetylenic lipid. 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . (canceled) 
     
     
         45 . The method of  claim 41  wherein the microbubbles are treated with UV for at least 30 minutes to polymerize the polymerizable lipid. 
     
     
         46 . (canceled)